The macrolactins are a group of natural products isolated from a bacterium native to the deep ocean floor. Macrolactin A was tested by the National Cancer Institute and found to control human HIV replication using human T-lymphoblast cells at a concentration of 10 mg/mL. Macrolactin A was also found to have significant antiviral and cancer cell cytotoxic properties. These tantalizing results should be followed by a through investigation of macrolactin A in related HIV and anticancer screening programs as well as acute toxicity testing. Unfortunately there is no more macrolactin A, and it cannot be produced by fermentation at this time, so further exploration of its potential in human medicine awaits its synthesis. The goal of this proposal is to synthesize sufficient quantities of macrolactin A for further testing. A secondary goal is to prepare isostructural analogs of macrolactin A to identify the structural features required for activity. The structure of macrolactin A is known but not the stereochemistry, so the first step will be to determine its stereochemistry. The synthesis is designed around a convergent approach to polyols and should lead to an efficient and stereoselective synthesis of macrolactin A. Synthesis of macrolactin A analogs involves replacing the diene subunits with isostructural aromatic residues. Because the route to macrolactin A is highly convergent, the analogs will be available by replacing advanced intermediates in the synthesis. These investigations will allow a realistic assessment to be made of macrolactin A's potential in AIDS therapy and other areas of human medicine.